The increasingly widespread use of meditation for stress-related emotional and medical conditions highlights the urgent need to rigorously evaluate mechanisms through which the benefits of practice might be conferred. Primary challenges in this regard include evaluating dose response relationships between practice time and outcomes; clarifying whether physiological and behavioral effects of meditation derive primarily from non-specific aspects of training or result from specific meditation practices; and identifying molecular mechanisms by which meditation might affect physiological responses relevant to stress-related illness. Recent findings from a cross-sectional study by our group indicate that young adults who are randomized to, and practice, compassion meditation demonstrate reduced inflammatory responses, less emotional distress, and reduced autonomic responses to a standardized laboratory psychosocial stressor (Trier Social Stress Test [TSST]) when compared to subjects randomized to an active control condition. However, as a result of the cross-sectional study design and lack of a meditation comparator arm, these results provide only partial insight into key issues outlined above regarding the role played by specific meditation procedures and/or practice time in observed physiological and behavioral outcomes. The primary hypothesis of the proposed work is that practicing a meditation procedure specifically designed to enhance empathic concern for others (i.e. compassion meditation) will optimize autonomic reactivity to psychosocial stress in a manner that results in diminished activation of peripheral inflammatory signaling pathways and reduced behavioral distress. To test this hypothesis, the following aims are proposed: Aim 1: to use a longitudinal design to definitively establish that practice time contributes to the effect of compassion meditation on in vivo inflammatory and behavioral responses to psychosocial stress; Aim 2: To examine whether the effect of compassion meditation on behavioral and inflammatory responses to psychosocial stress results specifically from training in the generation of empathic concern for others or derives more generally from learning the basic meditative practices of focused attention and mindfulness; and Aim 3: to investigate autonomic mechanisms by which meditation may attenuate stress-induced inflammation. To accomplish these aims, the current study will randomize 360 medically healthy adults to 6 weeks of either compassion meditation training, Mindful Attention Training (to control for exposure to the basic meditation practices of attention and mindfulness) or a health education discussion group (to control for potential non-specific elements such as group support). Prior to, and upon completion of these interventions, all subjects will undergo TSST testing in order to assess inflammatory, autonomic and behavioral responses to psychosocial stress. Health-relevant behavioral and lifestyle factors will also be assessed to evaluate their contribution to the effect of meditation on inflammation. The long-term health implications of this study will likely be far reaching given evidence that inflammatory pathways represent an important mechanism by which stress promotes and/or worsens many medical and psychiatric conditions. PUBLIC HEALTH RELEVANCE: The increasing use of meditation as a treatment for a variety of stress-related medical conditions highlights the public health importance of identifying mechanisms by which meditation may improve health, both to confirm efficacy for this widely used intervention and to better identify disease states toward which meditation might be optimally applied. The proposed study will test the hypothesis that meditation reduces inflammatory responses to psychosocial stress via reductions in autonomic activation in the face of perceived psychosocial stress. If confirmed, the long-term health implications of this hypothesis would likely be far reaching, given evidence that activation of innate immune inflammatory pathways represents an important mechanism by which stress promotes and/or worsens a wide range of serious medical and psychiatric conditions (i.e. vascular disease, diabetes, cancer, HIV, major depression) to which meditation is being increasingly applied as an intervention.